Department of Mathematics, Near East University, Nicosia, Cyprus.
Mathematics Research Center, Near East University, Nicosia, Cyprus.
Sci Rep. 2023 Aug 1;13(1):12426. doi: 10.1038/s41598-023-38814-2.
This paper addresses the dynamics of lung cancer by employing a fractional-order mathematical model that investigates the combined therapy of surgery and immunotherapy. The significance of this study lies in its exploration of the effects of surgery and immunotherapy on tumor growth rate and the immune response to cancer cells. To optimize the treatment dosage based on tumor response, a feedback control system is designed using control theory, and Pontryagin's Maximum Principle is utilized to derive the necessary conditions for optimality. The results reveal that the reproduction number [Formula: see text] is 2.6, indicating that a lung cancer cell would generate 2.6 new cancer cells during its lifetime. The reproduction coefficient [Formula: see text] is 0.22, signifying that cancer cells divide at a rate that is 0.22 times that of normal cells. The simulations demonstrate that the combined therapy approach yields significantly improved patient outcomes compared to either treatment alone. Furthermore, the analysis highlights the sensitivity of the steady-state solution to variations in [Formula: see text] (the rate of division of cancer stem cells) and [Formula: see text] (the rate of differentiation of cancer stem cells into progenitor cells). This research offers clinicians a valuable tool for developing personalized treatment plans for lung cancer patients, incorporating individual patient factors and tumor characteristics. The novelty of this work lies in its integration of surgery, immunotherapy, and control theory, extending beyond previous efforts in the literature.
本文通过采用分数阶数学模型研究手术和免疫疗法联合治疗的方法,探讨了肺癌的动力学。本研究的意义在于探讨手术和免疫疗法对肿瘤生长速度和对癌细胞免疫反应的影响。为了根据肿瘤反应优化治疗剂量,利用控制理论设计了一个反馈控制系统,并利用庞特里亚金极大值原理推导出最优性的必要条件。结果表明,繁殖数 [Formula: see text]为 2.6,这意味着肺癌细胞在其一生中会产生 2.6 个新的癌细胞。繁殖系数 [Formula: see text]为 0.22,这意味着癌细胞的分裂速度是正常细胞的 0.22 倍。模拟结果表明,与单独治疗相比,联合治疗方法显著改善了患者的预后。此外,分析还强调了稳态解对 [Formula: see text](癌细胞干细胞分裂率)和 [Formula: see text](癌细胞干细胞分化为祖细胞的比率)变化的敏感性。这项研究为临床医生为肺癌患者制定个性化治疗计划提供了一个有价值的工具,将个体患者因素和肿瘤特征纳入其中。这项工作的新颖之处在于它将手术、免疫疗法和控制理论结合在一起,超越了文献中的先前研究。